The major goal of the proposed research is to understand how growth is controlled in livestock animals. Three hormones known to be involved in growth control are growth hormone (GH), growth hormone releasing factor (GRF), and insulin-like growth factor I (IGF-I). During the past three years it has become possible to introduce new genes into large animals and thus to study the effect of the products of these genes on the animal. These animals are called transgenic. The three specific aims of the proposed research are:
Specific Aim 1 : To achieve high level expression of GH, GRF and IGF-I transgenes in sheep, pigs and cows.
Specific Aim 2 : To study the effects of these transgenes on growth and development of each species.
Specific Aim 3 : To develop gene constructs with a higher level of expression and better transcriptional control through pilot studies in mice and rabbits and subsequent testing in larger animals. Several lines of animals in each of the three large animal species will be produced that express each of the three growth-related genes. Fusion genes in which heterologous promoter/regulators are connected to the growth genes will be used to achieve and control expression of the individual genes. This will create lines of animals in which the blood levels of the hormones resulting from the new genes are elevated and ideally may be regulated by external experimental factors. These animals will provide unique models to understand how each of these hormones influences the growth and physiology of animals in each species. The proposed studies have considerable relevance to major biological questions, and the results will benefit livestock producers. The ability to control the growth of large animals would be of enormous value to the farm economy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019018-05
Application #
3316180
Study Section
Reproductive Biology Study Section (REB)
Project Start
1984-07-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Theisen, M; Behringer, R R; Cadd, G G et al. (1993) A C/EBP-binding site in the transferrin promoter is essential for expression in the liver but not the brain of transgenic mice. Mol Cell Biol 13:7666-76
Rexroad Jr, C E; Mayo, K; Bolt, D J et al. (1991) Transferrin- and albumin-directed expression of growth-related peptides in transgenic sheep. J Anim Sci 69:2995-3004
Palmiter, R D; Sandgren, E P; Avarbock, M R et al. (1991) Heterologous introns can enhance expression of transgenes in mice. Proc Natl Acad Sci U S A 88:478-82
Lo, D; Pursel, V; Linton, P J et al. (1991) Expression of mouse IgA by transgenic mice, pigs and sheep. Eur J Immunol 21:1001-6
Guthrie, H D; Pursel, V G; Miller, K F et al. (1991) Effect of bovine growth hormone gene expression, sex and age on plasma gonadotropins, estrone and testosterone in prepuberal pigs. Domest Anim Endocrinol 8:423-9
Doi, T; Striker, L J; Gibson, C C et al. (1990) Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I. I. Relationship between increased glomerular size and mesangial sclerosis. Am J Pathol 137:541-52
Frohman, L A; Downs, T R; Kashio, Y et al. (1990) Tissue distribution and molecular heterogeneity of human growth hormone-releasing factor in the transgenic mouse. Endocrinology 127:2149-56
Pursel, V G; Bolt, D J; Miller, K F et al. (1990) Expression and performance in transgenic pigs. J Reprod Fertil Suppl 40:235-45
Pursel, V G; Hammer, R E; Bolt, D J et al. (1990) Integration, expression and germ-line transmission of growth-related genes in pigs. J Reprod Fertil Suppl 41:77-87
Brar, A K; Brinster, R L; Frohman, L A (1989) Immunohistochemical analysis of human growth hormone-releasing hormone gene expression in transgenic mice. Endocrinology 125:801-9

Showing the most recent 10 out of 24 publications